Thread by @KateWassum

New paper out from our lab:
I asked @MelissaMalvaez to come up with a simple side project…
...she ended up discovering a molecular director of habit.
Here’s what she found. Thread👇
biologicalpsychiatryjournal.com/article/S0006-…

Free for 50 days:
authors.elsevier.com/a/1XYUd1S07YLQ5

When you do something repeatedly and it always leads to a positive outcome, eventually you don’t need to think about it anymore, you just do it when the circumstance arises. This is a habit.

Habits are important. Think walking or riding a bike. But you don’t want them to develop too fast, this can lead to bad habits.

HDACs are epigenetic transcriptional repressors. When they are in place at a gene’s promoter they, generally, prevent that gene from being expressed.

But they can be removed by salient events, e.g., a learning experience, to promote the gene transcription that allows the long-term brain changes underlying behavioral change.

.@MelissaMalvaez found if she inhibited Class 1 HDACs she made subjects form habits faster. She narrowed this effect to HDAC3 in dorsal striatum. Thus our title: Habits are negatively regulated by HDAC3 in the dorsal striatum.

Basically, in the dorsolateral and dorsomedial striatum HDAC3 acts like a gate for habit.

HDAC3 remains in place at the promotors of some key plasticity genes (gate shut) to preserve cognitive control of behavior and prevent habits.

But when until enough successful repetition has occurred to ensure sufficient accuracy of the habit, HDAC3 can be removed from these gene promotors (gate open) to allow habit.

It was surprising that this was the case in *both* the lateral and medial dorsal striatum. We knew the lateral is important for habit. But the medial has been canonically implicated in the opposing cognitive strategy- actions, not habits.

What does this mean/why should you care?

Well, if HDAC3 were to get screwed up… say by stress or drug exposure… then this could cause one to form habits when it’s not adaptive, i.e., bad habits. That’s important to know if we want to treat mental illnesses marked by compulsive habits.

This is also important info for conditions where there is trouble with good habits, e.g., walking.

Huge thx to @pjokennedy and Marcelo Wood labs. Their collaboration was CRUCIAL!!!